It is proposed to investigate newly discovered non-neuronal functions of acetylcholine in two areas involving the eye; (a) in glaucoma and (b) in the cornea: (a) Recent research has established that the muscarinic effect of ACh on certain cell types is mediated by a rise in cellular cyclic guanosine monophosphate, which is blocked by corticosteroids. This cellular response to both ACh and to steroids parallels the ocular pressure responses to these drugs, i.e. steroids induce a rise in pressure and muscarinic agonists decrease the elevated pressure. This evidence suggests that GMP may be involved in the cholinergic drug response as well as in the etiology of chronic simple glaucoma. Levels of ACh and c-GMP will be determined in aqueous humor from normal and glaucomatous human eyes and in rabbit eyes pretreated with cholinergic drugs and anticholinesterases. (b) Important physiological funcpions for ACh are suggested by the unusually large amounts found in the corneal epithelium. Circumstantial evidence indicates that epithelial cells are subject to a growth regulating mechanism, involving ACh and possibly c-GMP, which is inhibited by corticosteroids and by interference with the corneal nerves. Levels of ACh, c-GMP and choline acetyl-transferase will be studied in the corneal epithelium of humans and rabbits in relation to genetic variability, denervation, cellular growth rate, glaucoma and severity of dendritic keratitis in herpes simplex virus infections. The research program will investigate the involvement of c-GMP in the lowering of ocular pressure by cholinergic drugs, and whether chronic simple glaucoma is associated with a defect in enzymatic systems regulating c-GMp levels. This will open up new avenues for understanding the genetic basis of glaucoma, the cellular mechanisms involved in the rise of pressure, as well as new approaches to therapy. It will establish whether the high concentration of ACh present in the cornea has a trophic function on growth and integrity of the corneal epithelium.